Phase II Study of Maintenance Rucaparib in Patients With Platinum-Sensitive Advanced Pancreatic Cancer and a Pathogenic Germline or Somatic Variant in , , or .

PURPOSE

Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi), is approved as maintenance therapy for patients with advanced pancreatic cancer (PC) and a germline or pathogenic variant (PV). This investigator-initiated, single-arm phase II study assessed the role of the PARPi rucaparib as maintenance therapy in advanced PC with germline or somatic PV in , , or .

PATIENTS AND METHODS

Eligible patients had advanced PC; germline (g) or somatic (s) PVs in , , or , and received at least 16 weeks of platinum-based chemotherapy without evidence of platinum resistance. Chemotherapy was discontinued and patients received rucaparib 600 mg orally twice a day until progression. The primary end point was the progression-free survival (PFS) rate at 6 months (PFS6). Secondary end points included safety, ORR, disease control rate, duration of response, and overall survival.

RESULTS

Of 46 enrolled patients, 42 were evaluable (27 g, seven g, six g, and two s). PFS6 was 59.5% (95% CI, 44.6 to 74.4), median PFS was 13.1 months (95% CI, 4.4 to 21.8), and median overall survival was 23.5 months (95% CI, 20 to 27). The PFS at 12 months was 54.8%. ORR of the 36 patients with measurable disease was 41.7% (3 complete responses; 12 partial responses; 95% CI, 25.5 to 59.2), and disease control rate was 66.7% (95% CI, 49.0 to 81.4). Median duration of response was 17.3 months (95% CI, 8.8 to 25.8). Responses occurred in patients with (41%, 11 out of 27), (50%, 3 out of 6), and (50%, 1 out of 2). No new safety signals were noted.

CONCLUSION

Maintenance rucaparib is a safe and effective therapy for platinum-sensitive, advanced PC with a PV in , , or . The finding of efficacy in patients with g and s PVs expands the population likely to benefit from PARPi beyond g/ PV carriers.